Ocular Circulation Research Articles

Retinal branch artery occlusion following injection of hyaluronic acid (Restylane)

The authors report a retinal branch artery occlusion occurring after facial injection of a dermal filler. The superior temporal artery showed occlusion due to a clearly visible long and fragmented embolus suggestive of gel and clearly distinguishable from calcific or cholesterol emboli. The authors suppose that hyaluronic acid gel was embolized in the patient. The embolized material is supposed to enter the ocular circulation through retrograde arteriolar flow after intra-arterial injection into one of the peripheral branches of the ophthalmic artery. If there is any evidence of a visual problem after facial injection of a dermal filler, prompt consultation of an ophthalmologist is recommended.

Platelet-mediated thrombotic complications in patients with ET: Reversal by aspirin, platelet reduction, and not by coumadin

The broad spectrum of aspirin-sensitive erythromelalgia, its microvascular ischemic complications, migraine-like atypical or typical transient ischemic attacks (cerebral and ocular) as well as acute coronary syndromes in thrombocythemia vera (essential thrombocythemia and thrombocythemia associated with polycythemia vera in maintained remission by phlebotomy) is caused by platelet cyclo-oxygenase-mediated arteriolar inflammation, fibromuscular intimal proliferation without and with occlusive thrombosis by platelet-rich thrombi in the end-arterial microvasculature of the peripheral, cerebral, ocular and coronary circulation. These microvascular ischemic and thrombotic complications does not respond to Coumadin, but are immediately relieved by a loading dose of 500 mg aspirin, and does not recur when the patient is maintained on low dose aspirin (50 mg per day) or after reduction of platelet counts to normal (<400.000/μl).

Ocular Safety in Patients Using Sildenafil Citrate Therapy for Erectile Dysfunction

Sildenafil citrate improves erectile function in men with erectile dysfunction (ED) by selectively inhibiting cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), which is present in all vascular tissue. Sildenafil also has a weaker inhibitory action on PDE6, located in the rod and cone photoreceptors. Modest, transient visual symptoms, typically blue tinge to vision, increased brightness of lights, and blurry vision, have been reported with sildenafil use and occur more frequently at higher doses. Visual function studies in healthy subjects and in patients with eye disease suggest that sildenafil does not affect visual acuity, visual fields, and contrast sensitivity. Transient, mild impairment of color discrimination can occur around the time of peak plasma levels. Spontaneous postmarketing reports of visual adverse events, including nonarteritic anterior ischemic optic neuropathy (NAION), have been reported during the 7 years that sildenafil has been prescribed to more than 27 million men worldwide. However, because men with ED frequently have vascular risk factors that may also put them at increased risk for NAION, a causal relationship is difficult to establish. No consistent pattern has emerged to suggest any long-term effect of sildenafil on the retina or other structures of the eye or on the ocular circulation.

Effects of Ocular Circulation by Acupuncture Stimulation on the crus outside

Effects of Ocular Circulation by Acupuncture Stimulation on the crus outside

Ocular circulation in diabetic patients with coronary artery disease

To evaluate the ocular circulation in diabetic patients with coronary artery disease (CAD). Thirty diabetic patients with diabetic retinopathy of grade 20 or 35, as evaluated by the Early Treatment Diabetic Retinopathy Study, were studied. They were divided into those without CAD (15 cases) and those with CAD (over 75% stenosis of carotid artery; 15 cases). All underwent standard ophthalmic examinations and orbital color Doppler imaging. Fifteen healthy controls underwent the same examinations. The peak systolic velocity in the central retinal artery was significantly lower in the two diabetic groups. The end-diastolic velocity in the central retinal artery was significantly lower only in the diabetic patients with CAD. There were no significant intergroup differences in blood flow velocities in the ophthalmic artery, short posterior ciliary artery, and central retinal vein. The blood flow waves were flattened in the diastolic phase for all orbital arteries in significantly more eyes in the diabetic patients with CAD. Echocardiography, performed only in the diabetic patients with CAD, showed that 10 cases (67%) had reduced systolic functions and/or diastolic functions and/or asynergy of the left ventricle. A decrease in blood flow velocities in the diastolic phase was found in diabetic patients with CAD. The findings indicate that this is probably related to the decrease in cardiac output.

252 Ontogeny of VEGF, IGF-I, and GH in the Rat Retina, Vitreous and Serum

Background/Aim: Growth factors such as VEGF, IGF-I, and GH are implicated in retinal vascular development. Low serum IGF-I and high serum GH has been shown to be associated with ROP. The ocular compartments are protected by the blood-retinal barrier. We hypothesized that levels of growth factors in the ocular and systemic circulation are different and compartment-specific. We examine the ontogeny of VEGF, IGF-I and GH in rat retina, vitreous, and serum from birth (P0) to P21. Methods. Newborn rats (n=3 litters/group; 15 pups/litter) were sacrificed at P0, P7, P14 and P21. Retinal, vitreous and serum VEGF, IGF-I and GH levels were determined. Results: VEGF levels were 10-fold higher in the vitreous than serum at all stages of development. Vitreous and serum VEGF levels declined at P7, P14 and P21 (p<0.05 to p<0.001) compared to P0. In the retina, VEGF levels increased with highest concentrations at P21 (p<0.05 vs P0). IGF-I levels in the vitreous were comparable with serum levels and decreased from P7 through P21 (p<0.05) compared to P0. IGF-I levels in serum and retina increased with advancing postnatal age. Despite 4-fold higher IGF-I levels in the vitreous than retina at P0, equilibration was achieved at P21. GH levels in the vitreous were 10-fold lower than serum levels and were decreased at P14 and P21 (p<0.05 to p<0.001) compared to P0 and P7 in both compartments. GH levels in the retina remained unchanged from P0 through P21. Conclusions: The ontogenic patterns of vitreous VEGF and IGF-I during rat postnatal retinal development imply that the vitreous is a reservoir for these growth factors. VEGF, IGF-I and GH in the retina, vitreous and systemic circulation exhibit compartment-specific differences. These differences should be considered in conditions associated with retinal neovascularization, such as ROP.

Topical dorzolamide increases pericentral visual function in age‐related maculopathy: pilot study findings with short‐wavelength automated perimetry

Numerous studies have confirmed the enhancement of ocular circulation by carbonic anhydrase inhibitors (CAIs). Topical CAI treatment with dorzolamide averts the significant pericentral visual function loss accompanying retinal and choroidal vasoconstriction during acute hyperventilation-induced hypocapnia. This study was designed to discern whether dorzolamide might similarly enhance macular function in patients with age-related maculopathy (ARM). In a masked, placebo-controlled study, 40 patients with ARM and acuity > 20/50 were randomized to receive either dorzolamide or placebo for 12 weeks, thrice daily. After pre-study perimetric training, pericentral function (mean sensitivity) was quantified using Humphrey 10-2 short-wavelength automated perimetry (SWAP), before and after 12 weeks of topical therapy. Dorzolamide-treated eyes demonstrated a significant increase in mean sensitivity of + 1.55 dB (p = 0.04); placebo-treated eyes showed no significant change (+ 0.58 dB; p = 0.10). Given the non-significant increase of mean sensitivity in the placebo-treated group, fewer than 100 subjects per group would be required to afford > 70% power to yield a significant direct comparative difference between treatment and placebo in a prospective, randomized study of equally short duration. This study demonstrated a significant increase in short-wavelength sensitivity in ARM with dorzolamide and the lack thereof with placebo. These encouraging pilot study data suggest a potential role for topical CAIs in ARM patients, and establish objective parameters for prospective studies to further evaluate the effects of dorzolamide in ARM.

Bunazosin, a Selective α1 ‐Adrenoceptor Antagonist, as an Anti‐glaucoma Drug: Effects on Ocular Circulation and Retinal Neuronal Damage

Bunazosin hydrochloride is a potent and selective alpha1-adrenoceptor antagonist that has been clinically used both as a systemic antihypertensive as well as an ocular hypotensive drug. In a number of studies, we have examined some effects of bunazosin hydrochloride that might indicate its potential as an anti-glaucoma drug. In normal rabbit eyes, topically instilled bunazosin hydrochloride reached the posterior retina by local penetration at concentrations sufficient to attenuate the phenylephrine- or endothelin-1 (ET-1)-induced constriction of retinal arteries. Furthermore, bunazosin hydrochloride improved the impairment of optic nerve head (ONH) blood flow, the prolongation of visual-evoked potentials (VEP) implicit time, the enlargement of the optic disk cup, and the decrease in the number of retinal ganglion cell layer cells induced by repeated injections of ET-1 in rabbits. Topically instilled bunazosin hydrochloride improved the reductions in ONH capillary blood flow and VEP amplitude induced in rabbit eyes by nitric oxide synthase inhibition. In rat primary retinal cultures, bunazosin hydrochloride reduced glutamate-induced neuronal cell death, presumably through a Na+ channel blocking effect. In healthy humans, topically instilled bunazosin hydrochloride reportedly increases blood velocity in the ONH, retina and choroid, without significantly altering either blood pressure or heart rate. These results indicate that bunazosin hydrochloride exerts both an improvement effect within the ocular circulation and a direct neuroprotective effect. Hence, bunazosin hydrochloride may be useful as a therapeutic drug against ischemic retinal diseases (such as glaucoma and retinal vascular occlusive diseases) that are associated with disturbances of the ocular circulation.

Effects of Ocular Circulation by Acupuncture Stimulation on Guangming (GB37)

Effects of Ocular Circulation by Acupuncture Stimulation on Guangming (GB37)

The effect of ocular warming on ocular circulation in healthy humans.

To examine the effect of ocular warming on retinal blood flow (RBF) and subfoveal choroidal blood flow (CBF) in humans. Ocular warming was induced in 10 healthy volunteers using an ocular warming lamp for 10 minutes. The ocular surface temperature was measured before and after warming. The RBF in the retinal artery and vein and the CBF in the foveal region were examined with a retinal laser Doppler velocimetry system and a laser Doppler flowmeter, respectively. Ocular blood flow measurements were performed before and 3, 6, and 9 minutes after warming. The ocular surface temperature significantly increased just after warming and returned to baseline 10 minutes later. Three minutes after warming, the mean +/- SE RBF significantly increased in the retinal artery (14.2% +/- 3.5%, P = .01) and vein (15.8% +/- 3.6%, P = .006). Six minutes after warming, the RBF returned to baseline in the artery and vein. Three and 6 minutes after warming, the mean +/- SE CBF significantly decreased 16.6% +/- 4.2% and 24.2% +/- 4.7%, respectively (P = .001 for both). Nine minutes after warming, the measurements returned to baseline. The RBF increased and the CBF decreased in the foveal region after cessation of ocular warming in healthy young volunteers. The CBF in the foveal region may contribute to maintaining a constant retinal temperature in response to ocular warming.

Clinical Potential of Lomerizine, a Ca2+ Channel Blocker as an Anti‐Glaucoma Drug: Effects on Ocular Circulation and Retinal Neuronal Damage

Glaucoma is defined as an optic neuropathy with characteristic changes in the optic nerve head and ultimate loss of visual field. Previous studies have suggested that (a) mechanical damage due to raised intraocular pressure and (b) a compromised tissue circulation in the optic nerve head play significant roles in the development of glaucomatous damage in the optic nerve head. Recently, we found that lomerizine, a new Ca(2+) channel blocker, increased ocular circulation and protected neuronal cells against retinal neurotoxicity both in vitro and in vivo with minimal cardiovascular side effects. We examined the effect of lomerizine on the ocular circulation and compared it with those of other Ca(2+) channel blockers in normal rabbits and in rabbits with an endothelin-1-disturbed circulation in the optic nerve head. In anesthetized rabbits, lomerizine and the other Ca(2+) channel blockers increased the ocular circulation and also inhibited the hypoperfusion induced in optic nerve head tissue by an intravitreous injection of endothelin-1. Whereas the other Ca(2+) channel blockers produced changes in blood pressure and heart rate, the effects of lomerizine on these parameters were slight. In healthy humans, lomerizine increased blood velocity in the optic nerve head, without significantly altering blood pressure or heart rate. Moreover, lomerizine reduced retinal damage in rats both in vitro and in vivo, presumably through a Ca(2+) channel blocking effect via an action that may involve a direct protection of retinal neurons as well as an improvement in the ocular circulation. These results indicate that lomerizine may be useful as a therapeutic drug against ischemic retinal diseases (such as glaucoma and retinal vascular occlusive diseases) that involve a disturbance of the ocular circulation.

Effects of sildenafil on ocular perfusion demonstrated by color Doppler ultrasonography.

The aim of this study was to investigate the effects of sildenafil on ocular hemodynamics by color Doppler ultrasonography (CDU). In all, 38 patients with erectile dysfunction diagnosed by International Index of Erectile Function (IIEF) and Sexual Health Inventory of Men (SHIM) scores were included into the study. After taking 100 mg of oral sildenafil citrate, all patients underwent CDU examination of central retinal artery at 60 and 75 min and CDU examination of cavernosal artery at 20, 60 and 75 min. All of the side effects during and after the test were also recorded. The mean cavernous artery peak systolic flow velocity increased significantly after sildenafil. However, no significant change was determined in central retinal artery flow parameters including peak systolic flow velocity, end-diastolic flow velocity, resistive index, pulsatility index, volume and diameter. Five patients experienced ocular side effects. No significant change was observed in retinal artery CDU measurements of patients having ocular side effects. Sildenafil has no effect on ocular hemodynamics on the basis of CDU. Ocular side effects may be the result of other changes in retinal photoreceptors rather than the ocular circulation.

Diurnal variation in microcirculation of ocular fundus and visual field change in normal-tension glaucoma.

Diurnal variations in microcirculation of the ocular fundus in normal-tension glaucoma (NTG) were examined to compare with the normal control eyes. The correlation between progression of visual field impairment and diurnal variations in ocular circulation was also studied. The subjects were 12 patients with NTG and 12 normal controls. Blood pressure (BP), intraocular pressure (IOP), ocular perfusion pressure (OPP), and square blur rate (SBR), an index of microcirculation acquired by the laser speckle method, were measured at 9 a.m. (morning), 3 p.m. (afternoon), and 9 p.m. (night). Diurnal variations in SBR were tested using the Friedman test and Wilcoxon signed ranks test. On the other hand, diurnal variations in BP, IOP, and OPP were tested by the analysis of variance. The visual field was evaluated at the same time as determining diurnal variation and again about 9 months later to calculate the change. The correlation between variation ratio in SBR and the change in visual field was examined by simple regression. A significant decrease (P=0.04) was found in SBR at night, as compared with the morning value, in the optic nerve head (ONH) of NTG, although no significant diurnal variations were found in SBR either in the choroid-retina or in normal control eyes. Other parameters showed no significant diurnal variations. The larger diurnal variation was in SBR of the ONH, and the more exacerbated visual field impairment was (r=0.59, P=0.04). These findings suggest that diurnal variations in the microcirculation of the ONH may play a role in the progression of NTG.

Author reply

Thank you for the opportunity to reply to the letter from Drs. Geiser, Logean, and Petrig. They state that they are puzzled by the references we have cited in our article, 1 Yoshida A. Feke G.T. Mori F. Nagaoka T. Fujio N. Ogasawara H. Konno S. McMeel J.W. Reproducibility and clinical application of a newly developed stabilized retinal laser Doppler instrument. Am J Ophthalmol. 2003; 135: 356-361 Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar and suggest that we should have provided a historical review of the development of various implementations of the laser Doppler technique for assessment of the ocular circulation. Because our article is not a review article, we chose not to do that. Reference 9 that we cited 2 Feke G.T. Yoshida A. Schepens C.L. Laser based instruments for ocular blood flow assessment. J Biomed Opt. 1998; 3: 415-422 Crossref PubMed Scopus (37) Google Scholar is, in fact, a review paper that does chronicle the development of the technique and includes citations to 13 papers coauthored by Dr. Charles E. Riva. Two of those papers 3 Feke G.T. Riva C.E. Laser Doppler measurements of blood velocity in human retinal vessels. J Opt Soc Am. 1978; 68: 526-531 Crossref PubMed Scopus (96) Google Scholar , 4 Riva C.E. Feke G.T. Eberli B. Benary V. Bidirectional LDV system for absolute measurement of blood speed in retinal vessels. Appl Opt. 1979; 18: 2301-2306 Crossref PubMed Scopus (108) Google Scholar are the seminal papers that established the specific methodology that has led to all the current laser Doppler instruments used to measure blood flow in individual retinal vessels.

Heparin-induced antiheparin-platelet antibody associated with retinal venous thrombosis

Objective To report a case of a 33-year-old white woman in whom retinal venous thromboses developed secondary to heparin-induced antiheparin-platelet antibodies. Design Interventional case report. Methods The patient underwent complete ophthalmic and medical examinations. Laser Doppler measurement of retinal blood circulation also was performed. Intervention Prolonged anticoagulation with thrombin inhibitors and warfarin. Main outcome measures Visual symptoms, retinal appearance on clinical examination, and measurement of retinal blood flow by laser Doppler technique. Results The patient experienced a scotoma in the visual field of the left eye, left retinal venous thrombosis, decreased venous blood flow in the left eye, and heparin-induced antiheparin-platelet antibodies in serum. After intervention, the visual symptoms and retinal appearance improved, and retinal blood flow normalized. Conclusions Heparin-induced antiheparin-platelet antibody can lead to thrombosis of the ocular circulation. This index case, which is the first one ever reported in association with antiheparin-platelet antibodies, further illustrates the potential side effects of heparin and widens the spectrum of complications of heparin-induced thrombocytopenia (HIT) and HIT thrombosis syndrome (HITTS).

Isolated preparations of ocular vasculature and their applications in ophthalmic research

The purpose of this review is to outline the techniques and applications for isolated ocular vascular preparations and their significance to ophthalmic research. Various isolated ocular vascular preparations have been utilized in studies of ocular vascular biology, physiology and pharmacology, including work in both normal and diseased conditions. However, there is still significant potential for further studies to improve our understanding of the ocular circulation and its regulation. Experience has shown that there is no single preparation capable of addressing all of the questions that must be answered if a complete understanding of mechanisms of vascular regulation in the eye is to be achieved. Rather, it is necessary to select the appropriate preparation and techniques to address each individual question in the most appropriate manner. In this review, particular emphasis is placed on the applications for isolated ocular preparations and the relevance of such studies to our understanding of the pathogenesis of eye diseases involving the vasculature. Examples are given where therapeutic approaches in diabetes and glaucoma are assessed in terms of their impact on the vasoactive properties of the ocular vasculature.A significant heterogeneity is present in the different parts of the ocular vasculature, not only in the structural and functional properties of vessel itself, but also in terms of the tissue environment and innervation. A single vasoactive agent may also have different effects when applied to the inside or the outside of the same region of a vessel. The vasoactive response of the vascular system as a whole is what determines the rate of blood flow through the system, but this is regulated by a multitude of factors in different regions of the vascular network. Isolating individual components of the ocular vasculature is readily achievable for the extraocular vessels such as the ophthalmic or ophthalmocilliary arteries, which can be studied in myograph type systems measuring the mechanical vasoactive force generated by the vessel. Retinal vessels from very large animals can also be studied in this way, but the small diameter of the retinal vessels in most species requires a perfusion rather than myograph based technique. Perfusion based studies of vessel diameter in response to vasoactive stimuli can be applied to individual retinal arteries and their branches. Perfusion of more complex elements of the ocular vasculature such as isolated segments of the retina or ciliary body, or whole isolated perfused eyes may use the perfusate pressure as the determinant of vasoactive state. However, when several components of the ocular vasculature are being perfused simultaneously it may be difficult to separate out the contribution from the different vascular elements. The advantage of isolated preparations is that systemic influences can be eliminated, and vascular components can be studied that are inaccessible in vivo. The disadvantage is that no matter how well controlled the in vitro environment may be, it will always be a relatively poor mimic of the in vivo conditions. However, such in vitro work has certainly improved our understanding of the vasoactive properties of different regions of the ocular vasculature in both health and disease.

Methods for evaluation of curative effects of glaucomatous agents, especially the ocular circulation -improving effect

Methods for evaluation of curative effects of glaucomatous agents, especially the ocular circulation -improving effect

Effects of kallidinogenase on ocular tissue circulation in rabbits.

The purpose of this study is to evaluate the effects of kallidinogenase, a tissue kallikrein, on tissue circulation in the optic nerve head (ONH), choroid and retina. Kallidinogenase (1.0 IU/kg) or saline was injected intravenously into urethane-anesthetized rabbits, and the normalized blur value (NB), a quantitative index of in vivo tissue blood velocity, was measured in the ONH, choroid and retina before and for 90 minutes after injection, using the laser speckle method. The difference in NB values in the kallidinogenase group was significantly higher compared with that in the control group in the choroid (p < 0.05) and retina (p < 0.05, ANOVA of repeated measurements). In the ONH, however, there was no significant difference between the kallidinogenase group and the control group except transient increment 10 min after drug administration (p < 0.01, unpaired t-test). On the other hand, systemic condition parameters and intraocular pressure showed no intergroup difference significantly except for a transient decrease in blood pressure and increase in pulse rate in the kallidinogenase groups. Kallidinogenase increased blood velocity, and probably blood flow, in the choroid and retina of rabbits.

Retinal fluorescein contrast arrival time of young patients with the hepatosplenic form of the Schistosomiasis mansoni.

Schistosoma mansoni is responsible for lesions that can alter the hemodinamic of the portal venous circulation, lung arterial and venous sistemic systems. Therefore, hemodinamic changes in the ocular circulation of mansonic schistosomotic patients with portal hypertension and hepatofugal venous blood flow is also probable. The purpose of this study was to determine the fluorescein contrast arrival time at the retina of young patients with the hepatosplenic form of schistosomiasis, clinically and surgically treated. The control group included 36 non schistosomotic patients, mean age of 17.3 years, and the case group was represented by 25 schistosomotic patients, mean age of 18.2 years, who were cared for at The University Hospital (Federal University of Pernambuco, Brazil), from 1990 to 2001. They underwent digital angiofluoresceinography and were evaluated for the contrast arrival time at the early retinal venous phase of the exam. Both groups were ophthalmologically examined at the same hospital (Altino Ventura Foundation, Recife, Brazil), using the same technique. There was retardation of the retinal contrast arrival time equal or more than 70 sec in the eyes of three schistosomotic patients (12%) and in none of the control group, however, the mean contrast arrival time between the two groups were not statistically different. These findings lend support to the hypothesis that there could be a delay of the eye venous blood flow drainage.

New Laser Speckle Flowgraphy System Using CCD Camera

A new technique is developed to visualize the blood flow map of the human retina using laser speckle phenomena. Despite use of an ordinary CCD camera as the detector, the performance of laser speckle flowgraphy system for the analysis of ocular blood circulation is greatly improved to achieve higher resolution and a wider field of view for blood flow mapping. It is shown that the quality of the blood flow map is influenced by the sampling format of the pixel points in the space- and time-varying speckle field.